title: Association of 5-hydroxytryptamine (serotonin) receptor 4 (5-HTR4) gene polymorphisms with asthma.
abstract: OBJECTIVE
  The neurotransmitter, 5-hydroxytryptamine, acts as an immunomodulator by stimulating the release of inflammatory cytokines and regulating the function of dendritic cells and monocytes. The 5-hydroxytryptamine receptor 4 (HTR4) gene is located in a region previously linked to an increased risk of asthma and atopy. The aim of this study was to investigate the association between HTR4 and asthma.
  
  
  METHODS
  Thirty-two single nucleotide polymorphisms (SNP) in HTR4 were investigated by direct sequencing of 24 DNA samples from unrelated Korean subjects.
  
  
  RESULTS
  The 32 genetic variants comprised 22 intronic SNP, two SNP in the 3'-untranslated region (exon 7) and eight SNP in the 3'-downstream region. Logistic regression analysis showed that two intronic polymorphisms were significantly associated with the risk of asthma. Two minor HTR4 alleles, +142828G>A and +122769G>A, occurred at significantly higher frequencies in the asthmatic group than in the healthy control group (49.59% vs 42.29%, P=0.003, and 47.99% vs 40.35%, P=0.008, respectively), and these differences remained significant after correction for multiple testing (P=0.05, dominant mode of inheritance; and P=0.03, dominant mode, respectively). Haplotype analysis revealed three haplotype blocks. The frequency of haplotype 1 in block 2 was significantly higher in asthmatics (P=0.003, dominant mode), whereas the frequency of haplotype 4 in block 3 was significantly lower in asthmatics (P=0.0009, dominant mode).
  
  
  CONCLUSIONS
  SNP and haplotypes of the HTR4 gene were associated with the asthma phenotype and genetic variation of HTR4 may affect susceptibility to the development of asthma.
authors.affiliation: Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: An
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Cha
authors.forename: Eun-Kyong
authors.initials: EK
authors.lastname: Shin
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Sang-Hyuk
authors.initials: SH
authors.lastname: Yoon
authors.forename: Young-Mok
authors.initials: YM
authors.lastname: Lee
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Jong-Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Choi
authors.forename: Soo-Ok
authors.initials: SO
authors.lastname: Lee
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics*; D056910:Republic of Korea; D055815:Young Adult
chemical_list: D044422:Receptors, Serotonin, 5-HT4